The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function. 1. Sirtuins Sirtuins are a highly conserved family of proteins found in all organisms from yeast to mammals. All are orthologues of the yeast protein, silent information regulator 2 (Sir2) [1] and their primary targets are acetylated lysines of various peptides and proteins, including histones. Along with sequence homology, they also share functional similarities although the functions performed in mammals are more complex than in yeast, as reflected in the number of distinct orthologous forms. These play key roles in cellular stress and ageing, and as such, their function has been linked to diseases associated with ageing, including Alzheimer’s [2], Parkinson’s Disease [3], cancer [4], type II diabetes [5], and atherosclerosis [6]. Every member of the family contains a highly conserved core domain consisting of a NAD+-binding site and a catalytic domain [7]. Sirtuin function is tied to cellular energy production through nicotinamide adenine dinucleotide-(NAD+-) dependent deacetylation reactions, as well as o-ADP ribosylation, in response to changes in the cellular NAD+/NADPH ratio. Sirtuins appear to be involved in the extension of life span and health promotion in several species including yeast, nematodes and flies [8]. Pertinent to this is the observation that Sirtuins can be activated through caloric restriction, stress, or by pharmacological agents [9]. Sirtuins have a pivotal role in the expansion of lifespan in lower organisms via caloric
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